季铵化壳聚糖胰岛素纳米粒的制备、处方优化及其初步药效学实验

Preparation,formulation optimization and preliminary pharmacodynamic experiment of insulin-loaded N-trimethyl chitosan nanoparticles

目的采用正交设计试验优化载胰岛素季铵化壳聚糖纳米粒的处方工艺,并初步考察其降糖效果。方法用离子交联法制备载胰岛素的季铵化壳聚糖纳米粒,用正交试验确定其最佳处方工艺。用透射电子显微镜观察纳米粒的表面形态;用粒径/Zeta电位仪测定纳米粒的粒径和Zeta电位;用高效液相色谱(HPLC)法测定纳米粒的包封率、载药量及体外释放情况。对糖尿病大鼠皮下注射给药,对其药效学进行初步考察。结果制得的纳米粒呈球形,分布均匀;平均粒径(63.26±1.88)nm;Zeta电位(33.1±0.3)mV;包封率(37.92±2.11)%;载药量(5.42±0.3)%;24h累计释放率63.83%。皮下注射给药8h,糖尿病大鼠血糖较单纯注射胰岛素组下降平缓,且药效持久。结论优化后的载胰岛素的季铵化壳聚糖纳米粒形态较好、粒径较小,为研究胰岛素的新型给药途径奠定了基础。

Objective To prepare and optimize insulin-loaded N-trimethyl chitosan nanoparticles via orthogonal design , and preliminarily study the effects on blood glucose level .Methods The insulin-loaded N-trimethyl chitosan nanoparticles （INS-NPs） were prepared by ionic gelation ,and the optimal proportion was obtained with orthogonal design .The nanoparticles were characterized by transmission electron microscopy and zeta/sizer nano analyzer .The entrapment efficiency of insulin-load-ed nanoparticles and the in vitro releasing characteristics were studied by HPLC .A preliminary pharmacodynamic study of the insulin-loaded nanoparticles was also carried out .Results The INS-NPs exhibited narrow distribution .The mean diameter of INS-NPs was （63 .26 ± 1 .88）nm ,while the entrapment efficiency was （37 .92 ± 2 .11）% .After 8 hours of subcutaneous injec-tion of the INS-NPs ,the blood glucose level in diabetic rats decreased to normal level and kept stable .Conclusion The opti-mized insulin-loaded nanoparticles had homogeneous spherical shape ,small size ,and could be a new approach of administration for insulin .